Functions of glutaminyl cyclase and its isoform in diseases

Glutaminyl cyclase (QC; isoform: isoQC) is a zinc-dependent enzyme that catalyzes the intramolecular cyclization of N-terminal glutamine and glutamic acid residues into pyroglutamate residue (pGlu). This conversion type posttranslational modification called pyroglutamylation. The expression QC/isoQC regulated by epigenetics, cell homeostasis, its substrates. Pyroglutamylation an important maturation process during synthesis secretion hormones, functioning in different diseases, such as Alzheimer’s disease, tumors, other kinds chronic diseases mediated inflammation. IsoQC has been identified key regulator CD47-SIRPα checkpoint critical for pyroglutamylation CD47 at SIRPα binding site, thus helping cancer cells evade immune surveillance. Inhibition isoQC blocks interaction between SIRPα, leading to constrained tumor growth, indicating novel target immunotherapy. Targeting overcomes side effects targeting because Golgi resident not expressed on erythrocytes. Small molecules antibodies have developed isoQC, some them tested preclinical or clinical studies. Here, we briefly review discovery history then discuss regulation function emphasizing unique role Finally, summarize development inhibitors their progress trials with hope providing useful insights future investigation it various diseases.